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Notch-Delta-Jagged (NDJ) signaling among neighboring cells contributes crucially to spatiotemporal pattern formation and developmental decision-making. Despite numerous detailed mathematical models, their high-dimensionality parametric space limits analytical treatment, especially regarding local microenvironmental fluctuations. Using the low-dimensional dynamics of the recently postulated least microenvironmental uncertainty principle (LEUP) framework, we showcase how the LEUP formalism recapitulates a noisy NDJ spatial patterning. Our LEUP simulations show that local phenotypic entropy increases for lateral inhibition but decreases for lateral induction. This distinction allows us to identify a critical parameter that captures the transition from a Notch-Delta-driven lateral inhibition to a Notch-Jagged-driven lateral induction phenomenon and suggests random phenotypic patterning in the case of lack of dominance of either Notch-Delta or Notch-Jagged signaling. Our results enable an analytical treatment to map the high-dimensional dynamics of NDJ signaling on tissue-level patterning and can possibly be generalized to decode operating principles of collective cellular decision-making.
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http://dx.doi.org/10.1016/j.isci.2024.110569 | DOI Listing |
iScience
September 2024
Mathematics Department, Khalifa University, P.O. Box: 127788, Abu Dhabi, UAE.
Notch-Delta-Jagged (NDJ) signaling among neighboring cells contributes crucially to spatiotemporal pattern formation and developmental decision-making. Despite numerous detailed mathematical models, their high-dimensionality parametric space limits analytical treatment, especially regarding local microenvironmental fluctuations. Using the low-dimensional dynamics of the recently postulated least microenvironmental uncertainty principle (LEUP) framework, we showcase how the LEUP formalism recapitulates a noisy NDJ spatial patterning.
View Article and Find Full Text PDFNat Commun
March 2024
Georgetown University, Washington, DC, USA.
Chemotherapy and immune checkpoint inhibitors have a role in the post-neoadjuvant setting in patients with triple-negative breast cancer (TNBC). However, the effects of nivolumab, a checkpoint inhibitor, capecitabine, or the combination in changing peripheral immunoscore (PIS) remains unclear. This open-label randomized phase II OXEL study (NCT03487666) aimed to assess the immunologic effects of nivolumab, capecitabine, or the combination in terms of the change in PIS (primary endpoint).
View Article and Find Full Text PDFJ Clin Med
January 2024
Department of Cardiology, Copenhagen University Hospital-Herlev and Gentofte, 2900 Hellerup, Denmark.
Arrhythmogenic right ventricular cardiomyopathy is an inherited cardiomyopathy, characterized by abnormal cell adhesions, disrupted intercellular signaling, and fibrofatty replacement of the myocardium. These changes serve as a substrate for ventricular arrhythmias, placing patients at risk of sudden cardiac death, even in the early stages of the disease. Current echocardiographic criteria for diagnosing arrhythmogenic right ventricular cardiomyopathy lack sensitivity, but novel markers of cardiac deformation are not subject to the same technical limitations as current guideline-recommended measures.
View Article and Find Full Text PDFProstate Cancer Prostatic Dis
December 2024
P. Stradins Clinical University Hospital, Riga, Latvia.
Background: In patients with metastatic castration-resistant prostate cancer, darolutamide was well tolerated for 25 months, but minimal long-term safety data are available.
Methods: Treatment-emergent adverse events (TEAEs) for patients receiving darolutamide for a median of 38 months (n = 13) are described in this pooled analysis of individual patient data from phase 1/2 studies.
Results: All patients reported TEAEs (mostly grade 1/2).
J Allergy Clin Immunol
November 2023
Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Department of National Heart and Lung Institute, London.
Background: Allergen immunotherapy (AIT) is a well-established disease-modifying therapy for allergic rhinitis, yet the fundamental mechanisms underlying its clinical effect remain inadequately understood. Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy was a randomized, double-blind, placebo-controlled trial of individuals allergic to timothy grass who received 2 years of placebo (n = 30), subcutaneous immunotherapy (SCIT) (n = 27), or sublingual immunotherapy (SLIT) (n = 27) and were then followed for 1 additional year.
Objective: We used yearly biospecimens from the Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy study to identify molecular mechanisms of response.